There are three isoforms of nonmuscle myosin heavy chain (NMHC), II-A, II-B and II-C. The function of nonmuscle myosin II-C remains unclear though the mutation (R726S) in human nonmuscle myosin II-C result in hearing loss. Using homologous recombination we generated nonmuscle myosin II-C mutant (R726S) mice, and about 40% of the knock-in mice developed a lymphoproliferative disease at 3-5 months old. The sick mice exhibited enlarged lymph nodes, spleens and thymuses and accumulated lymphoblasts in a number of organs. The tumor invaded other tissues. By FACS analysis the lymphocytes from sick mice have a large number of cells that co-express T cell marker and B cell markers, but a second line of mice generated using a different strain of embryonic stem cells fail to show any abnormalities to date. We are trying to regenerate the original mice to see if they will develop the disease, and also we are crossing the sick mice to MRL/MpJ #000486 mice which should allow full expression of the autoimmune abnormalities.